The mission of the Breast Cancer Program (BC) is to conduct high-impact breast cancer research through collaborations among its members and with members of other Cancer Center programs. With a portfolio of basic, translational, clinical and population-based research, BC focuses on three broad themes: Theme 1 is focused on understanding mechanisms of responsiveness to endocrine therapy. Key accomplishments in this theme include the award of a Center for Cancer Systems Biology that supported development of the first roadmap for mathematically modeling estrogen receptor signaling (Clarke). Theme 2 elucidates nutritional, environmental and genetic risk factors of breast cancer susceptibility. Noteworthy accomplishments include demonstrating the role of epigenetic modifications in establishing and maintaining transgenerational mammary cancer susceptibility in rats (Hilakivi-Clarke). Theme 3 explores clinical, therapeutic, molecular, and social factors that impact the treatment and progression of breast cancer. Key accomplishments include a study led by Swain that changed clinical practice by showing the survival benefit of adding pertuzumab to standard therapy in metastatic HER2 positive breast cancer. Led by Robert Clarke, PhD, DSc, and Claudine Isaacs, MD, the Program has 24 members representing eight Georgetown University departments and two MedStar hospitals. The Program also includes 10 breast cancer patient advocates. From 2009 to 2012, 42 therapeutic trials have accrued 231 patients. BC research is highly collaborative and interdisciplinary, and would not be possible outside of a Cancer Center that adds value through substantial institutional support ($11.6M) and access to nine state-of-the-art Shared Resources, all of which are used by BC members. Members are supported by $5.1M in peer-reviewed funding (direct cost), including $3.1 M of direct NCI funding. BC is home to three multi-investigator grants. Productivity is demonstrated by 357 cancer-related, peer-reviewed publications, of which 35% are intra- and/or interprogrammatic, the latter including collaborators from all three other Programs. 52% of publications involve external collaborations. Additional noteworthy features include: a strong junior investigator mentorship program; development of novel investigator-initiated clinical trials across MWHC and MGUH with correlative studies using cellular reprogramming and functional genomic technologies; and outreach and research initiatives in the Black and Hispanic communities within our catchment area.